Summary Development of the mammalian lymphatic vasculature is a stepwise process requiring the specification of lymphatic endothelial cell progenitors in the embryonic veins, and their subsequent budding to give rise to most of the mature lymphatic vasculature. In mice, formation of the lymphatic vascular network starts inside the cardinal vein at around E9.5 when a subpopulation of venous endothelial cells get committed into the lymphatic lineage by their acquisition of Prox1 expression. Here we will continue with our long-time efforts to accomplish a detailed cellular and molecular characterization of the genes and mechanisms regulating the early steps leading to the formation of the mammalian lymphatic vasculature. A better understanding of basic aspects of early lymphatic development and the availability of novel tools and animal models has been instrumental in the identification of important novel functional roles of the lymphatic vasculature.